The highly contagious influenza virus is the major contributor to acute respiratory infections. Conventional influenza vaccines contain inactivated microorganisms or live-attenuated microorganisms. Disadvantages of such vaccine preparations include difficulty in large-scale production, safety considerations in handling and production, and the risks involved in immunizing elderly or immunodeficient individuals with live-attenuated vaccines.
Subunit vaccines, which utilize isolated components of a virus particle, have been developed as a safer alternative to conventional vaccines (Arnon). The components are typically recombinant proteins or synthetic short peptides. Influenza subunit vaccines, containing the surface proteins HA (haemagglutinin) and NA (neuraminidase), have proven to be less toxic than inactivated whole virus but of inferior protective capacity and immunogenicity (Engelhard, Potter). In particular, subunit vaccines have been ineffective in eliciting a CTL (cytotoxic T-lymphocyte) response (Arnon). The CTL response stimulates the production of T-lymphocytes, which attack cells perceived as abnormal, including virus-infected cells. Soluble subunit vaccines generally elicit only the humoral immune response, which stimulates B-lymphocytes to produce antibodies. Such a response is effective in attacking bacteria and viruses in the extracellular media, but not in the elimination of intracellular bacteria, parasites and virus-infected cells.
It is therefore desirable to provide an improved subunit influenza vaccine, which can elicit a strong humoral and CTL immune response without adverse side effects. In addition to producing an immediate immune response, an ideal vaccine should also provide a long-lived protective effect without the need for frequent booster doses.